Methods for administration of colchicine with grapefruit juice

Abstract

Methods for safe administration of colchicine together with consumption of grapefruit juice are disclosed.

1 . A method of administering colchicine to a patient in need thereof, comprising administering a daily dosage amount of colchicine orally to a patient consuming a daily amount of grapefruit juice that does not exceed about 16 fluid ounces. 
     
     
         2 . The method of  claim 1  wherein the colchicine is administered to the patient to prevent gout flares. 
     
     
         3 . The method of  claim 2 , wherein the daily dosage amount of colchicine is about 0.6 mg to about 1.2 mg. 
     
     
         4 . The method of  claim 1  wherein the colchicine is administered to the patient to treat an acute gout flare. 
     
     
         5 . The method of  claim 4 , wherein the daily dosage amount of colchicine is about 1.2 mg followed by about 0.6 mg after about an hour. 
     
     
         6 . The method of  claim 4 , wherein the daily dosage amount of colchicine is about 1.8 to about 4.8 mg. 
     
     
         7 . The method of  claim 1  wherein the colchicine is administered to the patient to treat familial Mediterranean fever. 
     
     
         8 . The method of  claim 7 , wherein the daily dosage amount of colchicine for an adult patient is about 1 to about 3 mg. 
     
     
         9 . The method of  claim 7 , wherein the daily dosage amount of colchicine for a child patient is about 0.25 mg to about 3 mg. 
     
     
         10 . The method of  claim 1 , further comprising monitoring the patient for colchicine toxicity. 
     
     
         11 . The method of  claim 1 , wherein after administration of a 0.6 mg colchicine oral dosage form to human subjects on the fourth day of twice daily consumption of 8 fluid ounces of grapefruit juice, the logarithmic transformed area under the curve of colchicine plasma concentration measured as a function of time from time 0 to time t (AUC 0−t ) is within about 80% to about 125% of 8807 hr*ng/ml;
 the logarithmic transformed area under the curve of colchicine plasma concentration measured as a function of time from time 0 to time infinity (AUC 0−∞ ) is within about 80% to about 125% of 10500 hr*ng/ml; or   the logarithmic transformed maximum plasma concentration (C max ) of colchicine is within about 80% to about 125% of 2074 ng/ml.   
     
     
         12 . The method of  claim 1 , wherein after administration of a 0.6 mg colchicine oral dosage form to human subjects on the fourth day of twice daily consumption of 8 fluid ounces of grapefruit juice, the colchicine oral dosage form is bioequivalent to the colchicine oral dosage form administered without consumption of grapefruit juice. 
     
     
         13 . The method of  claim 12 , wherein the upper and lower limits of the 90% confidence interval of a ratio of a geometric mean of logarithmic transformed area under the curve of colchicine plasma concentration measured as a function of time from time 0 to time infinity (AUC 0−∞ ) of the 0.6 mg colchicine oral dosage form administered alone to that administered on the fourth day of twice daily consumption of 240 mL of grapefruit juice are about 0.80 to about 1.25. 
     
     
         14 . The composition of  claim 12 , wherein the upper and lower limits of the 90% confidence interval of a ratio of a geometric mean of logarithmic transformed area under the curve of colchicine plasma concentration measured as a function of time from time 0 to time t (AUC 0−t ) of the 0.6 mg colchicine oral dosage form administered alone to that administered on the fourth day of twice daily dosing of 240 mL of grapefruit juice are about 0.80 to about 1.25. 
     
     
         15 . The composition of  claim 12 , wherein the upper and lower limits of the 90% confidence interval of a ratio of a geometric mean of logarithmic transformed maximum plasma colchicine concentration (C max ) of 0.6 mg colchicine administered alone to colchicine administered on the fourth day of twice daily dosing of 240 mL of grapefruit juice is about 0.7 to about 1.43.